2011
DOI: 10.1038/ijo.2011.232
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Role of mineralocorticoid receptor/Rho/Rho-kinase pathway in obesity-related renal injury

Abstract: OBJECTIVE:We examined whether aldosterone/Rho/Rho-kinase pathway contributed to obesity-associated nephropathy.SUBJECTS:C57BL/6J mice were fed a high fat or low fat diet, and mice on a high fat diet were treated with a mineralocorticoid receptor antagonist, eplerenone.RESULTS:The mice on a high fat diet not only developed obesity, but also manifested renal histological changes, including glomerular hypercellularity and increased mesangial matrix, which paralleled the increase in albuminuria. Furthermore, enhan… Show more

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Cited by 36 publications
(30 citation statements)
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“…Downregulation of vascular RhoA/ROCK signaling may contribute to impaired contractility in an endothelium-independent manner, as previously reported (40)(41)(42). This is unusual as well, because in the context of metabolic syndrome, obesity, or diabetes, animals displayed an increase in MR activity associated with increased ROCK activity (6,43,44). In addition, plasma aldosterone levels are increased in obese humans and animals with diabetes, whereas in Adipo-MROE mice, aldosterone plasma levels are unchanged, and MR overactivation is restricted to the adipocytes.…”
Section: Discussionmentioning
confidence: 73%
“…Downregulation of vascular RhoA/ROCK signaling may contribute to impaired contractility in an endothelium-independent manner, as previously reported (40)(41)(42). This is unusual as well, because in the context of metabolic syndrome, obesity, or diabetes, animals displayed an increase in MR activity associated with increased ROCK activity (6,43,44). In addition, plasma aldosterone levels are increased in obese humans and animals with diabetes, whereas in Adipo-MROE mice, aldosterone plasma levels are unchanged, and MR overactivation is restricted to the adipocytes.…”
Section: Discussionmentioning
confidence: 73%
“…Further, adipose tissue possesses its own renin-angiotensin-aldosterone system 7, 36 and more adipocytes could increase aldosterone production. Interestingly, it has been shown that the expression in the kidney of mineralocorticoid receptors was increased in mice fed a high fat diet 37 which could also contribute to sodium retention and increased blood pressure. Further, aldosterone may be involved in the modulation of insulin secretion and signaling 2, 38 contributing to the development of insulin resistance and diabetes.…”
Section: Discussionmentioning
confidence: 99%
“…A previous study of Dahl salt-sensitive rats indicated that increased oxidative stress promoted activation of the glomerular MR, and that eplerenone effectively restored urinary protein to normal levels [29]. Another study of C57BL/6J mice indicated that obesity and renal injury were associated with increased MR/Rho/Rho-kinase activity and that treatment with eplerenone inhibited these changes [30]. Taken together with other studies [31], it appears that oxidative damage leads to Rac1-induced activation of the MR and that this leads to renal injury.…”
Section: Discussionmentioning
confidence: 99%